Abstract

Endometriosis (EMS) is an estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides, which have profound biological functions, such as anti-cancer activities. However, the role and mechanism of ginsenosides and metabolites in endometriosis are completely unknown. Here, we found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that PPD promoted the expression of progesterone receptor (PR) and downregulated the expression of estrogen receptor α (ERα) in eESCs. Treatment with PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of estrogen on eESC autophagy. In addition, eESCs pretreated with PPD enhanced the cytotoxic activity of NK cells in response to eESCs. PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that PPD plays a role in anti-EMS activation, possibly by restricting estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by PPD or further structural modification.

Details

Title
The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity
Author
Zhang, Bing 1 ; Wen-Jie, Zhou 1 ; Chun-Jie Gu 1 ; Wu, Ke 1 ; Hui-Li, Yang 1 ; Mei, Jie 1 ; Jia-Jun, Yu 1 ; Xiao-Fan, Hou 1 ; Jian-Song, Sun 2 ; Feng-Yuan, Xu 3 ; Da-Jin, Li 1 ; Li-Ping, Jin 4 ; Ming-Qing, Li 5 

 Laboratory for Reproductive Immunology, Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China 
 National Research Centre for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, China 
 Wallace H.Coulter Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory School of Medicine, Georgia Institute of Technology, Atlanta, GA, USA 
 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China 
 Laboratory for Reproductive Immunology, Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China 
Pages
1-13
Publication year
2018
Publication date
May 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2054147254
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.